The main objective is to further elucidate the nucleocytoplasmic feed-back controls which regulate genetic expression and to determine the significance of differences in these controls in normal and neoplastic cells. Although a major emphasis will be placed on the nuclear post-transcriptional component, now most amenable to study, maximum information will be derived by extending the studies where technically feasible to include an assessment of the controls operating at the transcriptional level. Correlative studies will be carried out on normal and neoplastic tissues in vivo, or in culture and in cell-free systems now operational in this laboratory. Particular emphasis will be placed on the latter, which in combination with DNA:RNA hybridization will allow us to monitor directly the major portion of the feed-back controls operating between the nucleus and cytoplasm, to assess the reason for the abnormal distribution of RNA across the nuclear membrane of the cancer cell, and to test limited aspects of the current theories of carcinogenesis. BIBLIOGRAPHIC REFERENCES: Schumm, D.E. and Webb, T.E.: Modification of Nuclear Restriction In Vitro by Plasma from Tumor-bearing Animals. J. Natl. Cancer Inst. 54:123, 1975. Keefer, R.C., McNamara, D.J., Schumm, D.E., Billmire, D.F. and Webb, T.E.: Early Temporal Changes in Uridine Kinase Isozyme Profile of the Novikoff Hepatoma in Response to 5-Azacytidine. Biochem. Pharm. 24: 1287, 1975.